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Acetylcholinesterase Inhibitors as Pretreatment Before Acute Exposure to Organophosphates: Assessment Using Methyl-Paraoxon

[ Vol. 11 , Issue. 8 ]


Dietrich E. Lorke, Mohamed Y. Hasan, Syed M. Nurulain, Mohamed Shafiullah, Kamil Kuca and Georg A. Petroianu   Pages 1052 - 1060 ( 9 )


Prophylactic administration of reversible acetylcholinesterase (AChE) inhibitors can protect against the lethal effects of organophosphorus compounds (OPCs). The usefulness of pyridostigmine, the only compound approved by the Food and Drug Administration (FDA) for such pretreatment, has been questioned. In search for more efficacious alternatives, we have examined in vivo the efficacy of a group of ten compounds with known anti-AChE activity (pyridostigmine, metoclopramide, tiapride, ranitidine, physostigmine, tacrine, amiloride, methylene blue, 7- methoxytacrine and K-27) to reduce mortality induced by the OPC methyl-paraoxon. AChE inhibitors were given intraperitoneally in equitoxic dosage (25% of LD01) 30 min before OPC exposure. Protection was quantified in rats by determining the relative risk of death (RR) by Cox analysis, with RR=1 for animals given only methyl-paraoxon, but no pretreatment.

Only physostigmine (RR=0.39), K-27 (RR=0.40) and tacrine (RR=0.48) significantly (p≤ 0.05) reduced methylparaoxon- induced mortality, when given prophylactically. Pretreatment with pyridostigmine, ranitidine, tiapride, amiloride, metoclopramide and methylene blue did not significantly protect against the lethal effects of methyl-paraoxon. 7-methoxytacrine (7-MEOTA) significantly (p≤ 0.05) increased the relative risk of methyl-paraoxon-induced death (RR=1.31). These results indicate that pretreatment with pyridostigmine cannot be considered a broad-spectrum approach against OPC exposure. K-27 may be a suitable alternative if passage into the brain is contraindicated.


Carbamates, cholinesterase, Cox analysis, methyl-paraoxon, oximes, organophosphate, pretreatment, prophylaxis, rat, methyl-paraoxon-induced, Prophylactic administration.


College of Medicine, Florida International University, Department of Cellular Biology & Pharmacology, University Park GL 495 E, 11200 SW 8th St, Miami 33199, Florida, USA.

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